Medicinal Chemistry Perspectives on Drug Repurposing: Innovative Approaches and Therapeutic Breakthrough

Drug repurposing involves the discovery of new therapeutic uses of existing drugs that have already been approved by the regulatory authorities. It provides an alternative with more efficient approaches to traditional drug discovery, leveraging already known safety profiles, shortened development and financial costs. Current advances in computational biology, artificial intelligence and big-data analytics have expanded the range of opportunities for systematic repurposing, but the successful translation of these opportunities is increasingly dependent on the holistic input of medicinal chemistry. The therapeutic relevance of medicinal chemistry-guided repurposing is being investigated over a range of unmet medical conditions, such as complicated diseases, rare diseases and new health crises, such as the COVID-19 pandemic. In this review, we underscore the critical importance of medicinal chemistry, including structure-activity relationship analysis, molecular optimization, target engagement assay, and ADMET refinement, in supporting the efficacy and safety of repurposed candidates. We further discuss the co-existence of these strategies with in silico predictions of the target, virtual screening, and phenotypic assays to narrow down lead compounds and improve translational success. Additionally, the role of medicinal chemistry in personalized medicine is also taken into account, where special attention is paid to the possibility of modifying pharmacological characteristics to patient-specific molecular and biological phenotypes. The study aims to encourage researchers and clinicians to adopt the revolutionary potential of drug repurposing to enhance treatment decisions and overall health outcomes among a large number of patients. Moreover, in a medical landscape that is becoming more complex, drug repurposing can transform the pharmaceutical industry, accelerate the process of making viable therapy available, and facilitate the delivery of quality healthcare.